Surfactant Phospholipid Kinetics in Ventilated Children after Therapeutic Surfactant Supplementation.

Acute lung Injury leads to alterations in surfactant lipid composition and metabolism. Although several mechanisms contribute to dysregulated surfactant metabolism, studies investigating in vivo surfactant metabolism are limited. The aim of this study is to characterise surfactant phospholipid composition and flux utilising a stable isotope labelling technique in mechanically ventilated paediatric patients. Paediatric patients (<16 years of age) received 3.6 mg/kg intravenous methyl-D9-choline chloride followed by the endotracheal instillation of 100 mg/kg of exogenous surfactant after 24 h. Bronchioalveolar fluid samples were taken at baseline and 12, 24, 36, 48, 72 and 96 h after methyl-D9-choline infusion. Nine participants (median age of 48 days) were recruited. The primary phosphatidylcholine (PC) composition consisted of PC16:0/16:0 or DPPC (32.0 ± 4.5%). Surfactant supplementation resulted in a 30% increase in DPPC. Methyl-D9 PC enrichment was detected after 12 h and differed significantly between patients, suggesting variability in surfactant synthesis/secretion by the CDP-choline pathway. Peak enrichment was achieved (0.94 ± 0.15% of total PC) at 24 h after methyl-D9-choline infusion. There was a trend towards reduced enrichment with the duration of mechanical ventilation prior to study recruitment; however, this was not statistically significant (p = 0.19). In this study, we demonstrated the fractional molecular composition and turnover of surfactant phospholipids, which was highly variable between patients.

A scoping review: urinary markers of metabolic maturation in infants with CHD and the relationship to growth.

BACKGROUND: Growth failure in infants born with CHD is a persistent problem, even in those provided with adequate nutrition. OBJECTIVE: To summarise the published data describing the change in urinary metabolites during metabolic maturation in infants with CHD and identify pathways amenable to therapeutic intervention. DESIGN: Scoping review. ELIGIBILITY CRITERIA: Studies using qualitative or quantitative methods to describe urinary metabolites pre- and post-cardiac surgery and the relationship with growth in infants with CHD. SOURCES OF EVIDENCE: NICE Healthcare Databases website was used as a tool for multiple searches. RESULTS: 347 records were identified, of which 37 were duplicates. Following the removal of duplicate records, 310 record abstracts and titles were screened for inclusion. The full texts of eight articles were reviewed for eligibility, of which only two related to infants with CHD. The studies included in the scoping review described urinary metabolites in 42 infants. A content analysis identified two overarching themes of metabolic variation predictive of neurodevelopmental abnormalities associated with anaerobic metabolism and metabolic signature associated with the impact on gut microbiota, inflammation, energy, and lipid digestion. CONCLUSION: The results of this scoping review suggest that there are considerable gaps in our knowledge relating to metabolic maturation of infants with CHD, especially with respect to growth. Surgery is a key early life feature for CHD infants and has an impact on the developing biochemical phenotype with implications for metabolic pathways involved in immunomodulation, energy, gut microbial, and lipid metabolism. These early life fingerprints may predict those individuals at risk for neurodevelopmental abnormalities.

A Scoping Review: Urinary Markers of Metabolic Maturation in Preterm Infants and Future Interventions to Improve Growth.

Background: Growth failure in infants born preterm is a significant issue, increasing the risk of poorer neurodevelopmental outcomes and metabolic syndrome later in life. During the first 1000 days of life biological systems mature rapidly involving developmental programming, cellular senescence, and metabolic maturation, regulating normal growth and development. However, little is known about metabolic maturation in infants born preterm and the relationship with growth. Objective: To examine the available evidence on urinary markers of metabolic maturation and their relationship with growth in infants born preterm. Eligibility criteria: Studies including in this scoping review using qualitative or quantitative methods to describe urinary markers of metabolic maturation and the relationship with growth in infants born preterm. Results: After a screening process 15 titles were included in this review, from 1998-2021 drawing from China (n = 1), Italy (n = 3), Germany (n = 3), Greece (n = 1), Japan (n = 2), Norway (n = 1), Portugal (n = 1), Spain (n = 2) and USA (n = 1). The included studies examined urinary metabolites in 1131 infants. A content analysis identified 4 overarching themes relating to; (i) metabolic maturation relative to gestational age, (ii) metabolic signature and changes in urinary metabolites over time, (iii) nutrition and (iv) growth. Conclusion: The results of this scoping review suggest there are considerable gaps in our knowledge relating to factors associated with metabolic instability, what constitutes normal maturation of preterm infants, and how the development of reference phenome age z scores for metabolites of interest could improve nutritional and growth outcomes.

ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis.

PURPOSE: Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. METHODS: A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. RESULTS: 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations. CONCLUSIONS: Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance.

Where Should Critically Ill Adolescents Receive Care? A Qualitative Interview-Based Study of Perspectives of Staff Working in Adult and Pediatric Intensive Care Units.

PURPOSE: In the United Kingdom, critically ill adolescents are treated in either adult or pediatric intensive care units (AICUs or PICUs). This study explores staff perspectives on where and how best to care for this distinct group. MATERIALS AND METHODS: Semistructured interviews were conducted with 12 members of staff (3 medical, 6 nursing, and 3 allied health professionals) working in 4 ICUs; 2 general hospital AICUs and 2 tertiary centre-based PICUs in England. Interviews were audio-recorded, transcribed, and analyzed using framework analysis. FINDINGS: One overarching theme was identified, reflecting staff understanding of the term "adolescent," and this was linked to 2 further themes, each of which had several subthemes. "Needs of the critically ill adolescent" included medical needs, dignity and privacy, issues around consent, and the impact of intensive care admission. "Implications for staff" included managing parental presence and lack of familiarity, and emotional impact, of dealing with this patient group. Some of these factors are currently better accommodated in adult settings. CONCLUSIONS: Decision-making about the place of care should take into account the individual circumstances of the patient (e.g., nature of their medical condition and previous experiences, maturity, family preference) and not be based only on age at admission. We should work across disciplines to ensure we can discover, and consistently deliver, best practice to meet the needs of critically ill adolescents.

Preoperative bioelectrical impedance predicts intensive care length of stay in children following cardiac surgery.

We have previously shown that children with a bioelectrical impedance spectroscopy phase angle at 50° (PA 50°) of <2.7 on postoperative day 2 had a four-fold increase in the risk of prolonged paediatric intensive care length of stay. In this study, we demonstrate a relationship between a baseline measure of phase angle 200/5° and postoperative length of stay.

Eliciting the experiences of the adolescent-parent dyad following critical care admission: a pilot study.

Critically ill adolescents are usually treated on intensive care units optimised for much older adults or younger children. The way they access and experience health services may be very different to most adolescent service users, and existing quality criteria may not apply to them. The objectives of this pilot study were, firstly, to determine whether adolescents and their families were able to articulate their experiences of their critical care admission and secondly, to identify the factors that are important to them during their intensive care unit (ICU) or high dependency unit (HDU) stay. Participants were 14-17 year olds who had previously had an emergency admission to an adult or paediatric ICU/HDU in one of four UK hospitals (two adult, two paediatric) and their parents. Semi-structured interviews were conducted with eight mother-adolescent dyads and one mother. Interviews were transcribed and analysed using framework analysis. CONCLUSION: The main reported determinant of high-quality care was the quality of interaction with staff. The significance of these interactions and their environment depended on adolescents' awareness of their surroundings, which was often limited in ICU and changed significantly over the course of their illness. Qualitative interview methodology would be difficult to scale up for this group. What is known • Critically ill adolescents are usually treated on intensive care units optimised for older adults or younger children. • The way they access and experience health services may be different to most adolescent patients; existing quality criteria may not apply. What is new • Reported determinants of high-quality care were age-appropriateness of the environment, respectfulness and friendliness of staff, communication and inclusion in healthcare decisions. • The significance of these depended on adolescents' awareness of their surroundings, which was often limited and changed over the course of their illness.

The Accuracy of Noninvasive Peripheral Pulse Oximetry After Palliative Cardiac Surgery in Patients With Cyanotic Congenital Heart Disease.

BACKGROUND: Children with cyanotic congenital heart disease (CCHD) live with oxyhemoglobin saturations that are typically expressed as percentages in the range of 70s and 80s. Peripheral pulse oximetry (measurement of SpO2) performs poorly in this range and yet is widely used to inform clinical decisions in these patients. The reference standard is co-oximetry of arterial samples (SaO2). METHODS: In this study, 515 paired measurements of SpO2 and SaO2 were taken from 19 children who had undergone palliative cardiac surgery. RESULTS: SpO2 (Masimo SET LNCS Neo pulse oximeter) overestimated oxyhemoglobin saturation in 82% of measurements (mean 4.6% ± 6.6%). There was a strong negative correlation between mean bias and SaO2 ( r = -.96, P = .002, 95% confidence interval: -0.99 to -0.68). CONCLUSION: The results raise a concern that critical hypoxemia may go undetected and untreated if pulse oximetry is relied upon as the primary means of assessing oxyhemoglobin saturation in children with CCHD. Strong preference must be given to co-oximetry of arterial samples.

Accuracy of the Masimo SET® LNCS neo peripheral pulse oximeter in cyanotic congenital heart disease.

UNLABELLED: Introduction Non-invasive peripheral pulse oximeters are routinely used to measure oxyhaemoglobin saturation (SpO2) in cyanotic congenital heart disease. These probes are calibrated in healthy adult volunteers between arterial saturations of ~75 and 100%, using the gold standard of co-oximetry on arterial blood samples. There are little data to attest their accuracy in cyanotic congenital heart disease. Aims We aimed to assess the accuracy of a commonly used probe in children with cyanotic congenital heart disease. METHODS: Children with cyanotic congenital heart disease admitted to the Paediatric Intensive Care Unit with an arterial line in situ were included to our study. Prospective simultaneous recordings of SpO2, measured by the Masimo SET® LNCS Neo peripheral probe, and co-oximeter saturations (SaO2) measured by arterial blood gas analysis were recorded. RESULTS: A total of 527 paired measurements of SpO2 and SaO2 (using an ABL800 FLEX analyser) in 25 children were obtained. The mean bias of the pulse oximeter for all SaO2 readings was +4.7±13.8%. The wide standard deviation indicates poor precision. This mean bias increased to +7.0±13.7% at SaO2 recordings <75%. The accuracy root mean square of the recordings was 3.30% across all saturation levels, and this increased to 4.98% at SaO2 <75%. CONCLUSIONS: The performance of the Masimo SET® LNCS Neo pulse oximeter is poor when arterial oxyhaemoglobin saturations are below 75%. It tends to overestimate saturations in children with cyanotic congenital heart disease. This may have serious implications for clinical decisions.

Gas induction for pyloromyotomy.

BACKGROUND: Infants with pyloric stenosis are considered to be at high risk of aspiration on induction of anesthesia. Traditionally, texts have recommended classic rapid sequence induction (RSI) or awake intubation (AI). AI has generally fallen out of favor, while the components of RSI have become increasingly controversial. Infants are at high risk of hypoxemia if ventilation is not maintained while waiting for neuromuscular blockade to establish. The efficacy of cricoid pressure (CP) to prevent aspiration has not been proven. It can impair visualization of the glottis and make intubation difficult. It is debatable whether any RSI technique is needed for pyloromyotomy. A recent review of 235 infants reported no aspiration events. These children were anesthetized with a variety of techniques, including RSI, gas induction, and AI. In our institution, we teach a gaseous induction. The nasogastric tube is used to empty the stomach and anesthesia is induced with sevoflurane. A nondepolarizing muscle relaxant is administered and ventilation maintained until neuromuscular blockade is established and intubating conditions are optimal. We report our experience of this technique. METHOD: A retrospective medical notes review of all patients undergoing pyloromyotomy between 2005 and 2012. RESULTS: There were 269 patients (84.4% male, mean weight 3.74 kg ± 0.74). Two hundred and fifty-two (93.7%) received gas inductions and 17 (6.3%) intravenous (IV) inductions. Two children received an RSI. No patient-specific factors were identified to explain operator choice in those receiving IV inductions. There were no recorded aspiration events. CONCLUSION: Gas induction can be considered for children undergoing pyloromyotomy.

Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic--the risk of aerosol generation during medical procedures.

BACKGROUND: Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined 'aerosol generating procedures' (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures. METHODOLOGY/PRINCIPAL FINDINGS: This study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86-7.3 µm. Considering stages 2 (4-7.3 µm) and 3 (0.86-4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11-7.24) adjusted OR = 4.31 (0.83-22.5)). CONCLUSIONS/SIGNIFICANCE: With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83-22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.

Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF -238A polymorphism.

The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5' nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF -238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF -238A was significantly higher in patients who died in ICU compared to those who survived (p = 0.0063) as was the frequency of the two haplotypes LTA +252G, TNF -1031T, TNF -308G, TNF -238A and LTA +252G, TNF-1031T, TNF-308A and TNF-238A (p = 0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.

External validation of the SAPS II, APACHE II and APACHE III prognostic models in South England: a multicentre study.

OBJECTIVE: External validation of three prognostic models in adult intensive care patients in South England. DESIGN. Prospective cohort study. SETTING: Seventeen intensive care units (ICU) in the South West Thames Region in South England. PATIENTS AND PARTICIPANTS: Data of 16646 patients were analysed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared directly the predictive accuracy of three prognostic models (SAPS II, APACHE II and III), using formal tests of calibration and discrimination. The external validation showed a similar pattern for all three models tested: good discrimination, but imperfect calibration. The areas under the receiver operating characteristics (ROC) curves, used to test discrimination, were 0.835 and 0.867 for APACHE II and III, and 0.852 for the SAPS II model. Model calibration was assessed by Lemeshow-Hosmer C-statistics and was Chi(2 )=232.1 for APACHE II, Chi(2 )=443.3 for APACHE III and Chi(2 )=287.5 for SAPS II. CONCLUSIONS: Disparity in case mix, a higher prevalence of outcome events and important unmeasured patient mix factors are possible sources for the decay of the models' predictive accuracy in our population. The lack of generalisability of standard prognostic models requires their validation and re-calibration before they can be applied with confidence to new populations. Customisation of existing models may become an important strategy to obtain authentic information on disease severity, which is a prerequisite for reliably measuring and comparing the quality and cost of intensive care.